Transcript Slide 1

Optimizing Management of HIV:
Integrated Treatment for Depression
and Adherence
Focus area:
Increasing
Adherence to HIV
Medications
*
Life-Steps
• Psychoeducation/Motivation for
Adherence
• Getting to Appointments
• Communication with Treatment Team
• Coping with Side Effects
• Obtaining Medications
• Formulating a Daily Medication
Schedule
• Storing Medications
• Cue Control Strategies for Taking
Medication
• Guided Imagery/Rehearsal
• Handling Slips in Adherence
• Review
*Safren
SA, Otto MW, Worth J. Life-Steps: Applying cognitive behavioral
therapy to HIV medication adherence. Cogn Behav Pract. 1999;6:332-341.
Depression is Highly Prevalent
in Patients with HIV
• Rates of depression among
persons with HIV infection
range from 20-37% in
epidemiological and sample
studies (Atkinson & Grant, 1994; Bing et
al., 2001; Cruess et al., 2003)
• Depression is 2x more
prevalent in patients with
HIV than patients without
HIV (Cielsa & Roberts, 2001)
Why Target Depression in an HIV
Medication Adherence Study?
• Depression is associated with poor medication
adherence and accelerated disease progression
(Pence et al., 2007; Safren et al., 2001)
• Depressed patients are 3x more likely to be nonadherent to medical treatment regimens than nondepressed patients (DiMatteo et al., 2000)
• Depression may moderate the ability of a
patient to benefit from health-behavior
interventions that do not address depression
• HIV adherence interventions for individuals
with mental health disorders are lacking (Amico et
al., 2006; Simoni et al., 2006)
CBT for Adherence and
Depression (CBT-AD) in HIV
• Life-Steps (1 session)
• Psychoeducation/Motivational
Interviewing about CBT for
Depression (1 session)
• Behavioral Activation/Activity
Scheduling (1 session)
• Adaptive thinking (3 sessions)
• Problem Solving (3 sessions)
• Relaxation/Diaphragmatic
Breathing (1 session)
Each session builds on the previous session and
each session integrates adherence skills.
*
Life-Steps
• Psychoeducation/Motivation for
Adherence
• Getting to Appointments
• Communication with Treatment Team
• Coping with Side Effects
• Obtaining Medications
• Formulating a Daily Medication
Schedule
• Storing Medications
• Cue Control Strategies for Taking
Medication
• Guided Imagery/Rehearsal
• Handling Slips in Adherence
• Review
*Safren
SA, Otto MW, Worth J. Life-Steps: Applying cognitive behavioral
therapy to HIV medication adherence. Cogn Behav Pract. 1999;6:332-341.
Electronic Life Steps Workbook
Casey Claborn, M.S.
Thad R. Leffingwell,. Ph.D.
Department of Psychology
Oklahoma State University
Play Video
CBT-AD: Study 1
1. Two arm RCT (full CBT versus LifeSteps and provider
letter)
2. Cross over: those who still met initial inclusion criteria
could cross over from comparison group after post
3. Outcome: Adherence (MEMs), Depression
(Independent assessor, self-report)
CBT-AD Study 1: Sample Issues
>300 phone screens, 118 baseline evaluations
45 patients randomized (3 dropped post-randomization)
42 participants completed baseline and T2
29% AA, 15% Latino/Hispanic,
7% other; mean age = 44
64% had at least one additional DSM-IV diagnosis
38% had two additional DSM-IV diagnoses
Most frequent comorbid diagnoses (includes participants
with >1 comorbid diagnoses):
PTSD 13 (31%)
ADHD 2 (5%)
Social Phobia 9 (21%)
OCD 2 (5%)
Panic disorder 11 (26%)
GAD 2 (5%)
Study 1 Integrating the Treatment of Depression
†
with Adherence Counseling in HIV
• 2 Arm, cross-over design
comparing 12 sessions of CBTAD to a single session of
adherence counseling
• Participants: 45 randomized,
42 completers with DSM-IV
diagnosable depression
• CBT-AD resulted in improved
adherence (MEMS=pill cap)
and depression at 3 months,
and gains were maintained at
6 and 12 months.
• Those who “crossed over”
caught up after completing the
full intervention
MEMS Adherence outcomes
100
75
50
25
0
BASELINE
T2
CBT
ETAU
F(1,42) = 21.94, p< .0001, Effect size (Cohen d) = 1.0
HAM-D outcomes
25
20
15
10
5
0
BASE
T2
F(1,42) = 6.32, p < .02, Cohen d = .82
†Safren
SA, O’Cleirigh CO, Tan JY, et al. A randomized controlled trial of cognitive behavioral
therapy for adherence and depression (CBT-AD) in HIV-infected individuals. Health Psychol. 2009;28:1-10.
CBT-AD Study 2
Method
• CBT for Medication Adherence and Depression in
HIV+ Methadone Patients
o Participants recruited from methadone clinics and community
in Massachusetts and Rhode Island
o Randomized to either ETAU or CBT-AD
o Stratified by sex, depression severity (current MDD or residual
symptoms only), and adherence (baseline MEMS adherence
above or below 80%)
• Inclusion Criteria:
o HIV-positive
o Prescribed antiretroviral therapy
o History of injection drug use and
enrollment in a drug abuse
treatment program for at least
one month
o Current or subsyndromal
depression
o Between the ages of 18 and 65
Measures
Clinician-administered:
Self-report:
• Mini International
• Beck Depression InventoryNeuropsychiatric Interview
Short Form (BDI-SF; Beck et
(MINI; Sheehan et al., 1998)
al., 1961, 1988)
• Montgomery-Asberg
Depression Rating Scale
Biological Heath:
(MADRS; Montgomery &
• HIV plasma RNA viral load
Asberg, 1979)
• Clinical Global Impression • CD4+ lymphocyte count
(CGI; NIMH, 1985) for
Depression and Substance
Abuse Severity (1 = “Not at
all ill” to 7 = “Extremely ill)”
Measures
Adherence:
• Electronic pill-cap (Medication
Event Monitoring System,
MEMS; AARDEX)
• Monitored most
frequently dosed or
most difficult to remember
medication
• Non-adherence defined as
missed dose or dose late by
more than 2 hours
• Data corrected for pocketed
doses, etc.
Study Design &
Participant Flow Diagram
Baseline Diagnostic
Assessment (n = 154)
Baseline Independent
Assessment
Excluded (n = 65)
Did not meet
inclusion criteria
(n = 37)
Dropped out (n = 28)
Life-Steps (n = 89) and
Randomization
CBT-AD
(n = 44)
CBT-AD
(n = 45)
3 Month Assessment
(n = 41)
3 Month Assessment
(n = 40)
6 Month Assessment
(n = 35)
6 Month Assessment
(n = 38)
12 Month Assessment
(n = 36)
12 Month Assessment
(n = 30)
Participants
• 89 HIV-infected adults with a diagnosis of depression
in treatment for injection drug use were randomized
– Sex and Age
• 61% men, mean age = 47 (SD = 7)
– Substance Abuse Treatment
• 70% in methadone maintenance therapy, 6% in suboxone
therapy, 24% in group or individual substance abuse therapy
– Employment
• 66% on disability, 4% full-time work or school
– Race
• 49% White, 32% Black
– Ethnicity
• 25% self-identified as Hispanic or Latino
– Sexual Orientation
• 79% exclusively heterosexual
– Disease Characteristics at Baseline
• Mean CD4 = 449 (SD = 265), mean viral load = 3669 (SD = 13808)
– Exceptionally high psychiatric comorbidity
• 61% one additional DSM-IV diagnosis, 41% 2+
There were no significant differences between conditions for any of these variables.
CBT-AD had greater acute adherence outcomes:
Longitudinal (HLM) Analysis of MEMS
Acute MEMS Adherence Outcomes
85
ETAU
CBT-AD
80
75
70
65
10
9
8
7
6
3
3
3
t
os
(P
(R
iz
2
m
do
an
1
0
s
Vi
t)
en
tm
ea
Tr
n
io
at
it)
Improvement in the CBT-AD condition was
greater than in the ETAU condition (γslope =
0.717, t (87) = 2.01, p = .047).
CBT-AD had Better Acute Depression Outcomes:
Longitudinal (HLM) Analysis of BDI-13
Acute BDI Outcomes
ETAU
16
14
12
10
8
6
CBT-AD
0
1(
2
3
4
Ra
ndo
miz
atio
nV
isit
)
5
6
7
8
9
10
(
Po
st T
rea
tm
ent
)
Trajectory of improvement in self-reported depression was
greater for the CBT-AD condition than the ETAU
condition (γslope = -0.30, t (87) = -2.60, p = .01).
CBT Had Better Clinician-Assessed Depression
Outcomes: Analysis of CGI & MADRS
Post Treatment CGI Outcomes
Post Treatment MADRS Outcomes
31
5
Control
CBT-AD
4
29
Control
27
CBT-AD
25
23
21
3
19
17
2
Pre Randomization
Post Treatment
F = 14.77, df = (1,79), p < .001
15
Pre Randomization
Post Treatment
F = 6.52, df (1,79), p < .01
Follow-up Adherence Gains in CBT-AD
were not maintained after treatment ended
Follow Up MEMS Adherence Outcomes
80
CBT
75
ETAU
70
65
60
55
50
3 Month
6 Month
12 Month
Significant decrease in medication adherence across the follow-up time period
(γslope = -0.294, t (79) = -3.24, p < .01); and differences in adherence change
over the follow up time period did not differ significantly between the
conditions (γslope = 0.13, t (77) = -0.77, p = .44)
Depression Gains Were Maintained
After Treatment Ended
• The significant decreases in MADRS scores for the
CBT-AD condition and non-significant decrease in the
ETAU condition were maintained during the follow
up period
– A trend for a continuing decrease in depression symptoms
for the whole sample (γslope = -0.62, t (79) = -1.78, p = .08)
• The significant decreases in CGI scores for the CBTAD condition and non-significant decrease in the
ETAU condition were maintained during the follow
up period
– Continuing decrease in depression symptoms for the whole
sample (γslope = -0.10, t (79) = -2.29, p = .03)
Viral Load Did Not Differ by Study
Condition at Follow Up: Repeated Measures
(GLM) & Longitudinal (HLM) Analysis
• There were no significant differences between
the ETAU and CBT-AD conditions in HIV viral
loadlog 10 at post treatment (F (1,87) = 0.168, p = .85)
• After controlling for resistance and HIV viral
load at baseline, there was no significant
change in viral loadlog 10 during the course of the
study (γslope = -0.0015, t (84) = -0.801, p = .43) or significant
differences between conditions (γslope = -.0016, t (81)
= -0.450, p = .65) over the course of the study
CD4, However, Did Differ by Study
Condition at Follow Up: Repeated Measures
(GLM) & Longitudinal (HLM) Analysis
• There were no significant differences between
the ETAU and CBT-AD conditions in HIV viral
loadlog 10 at post treatment (F (1,87) = 0.168, p = .85)
• After controlling for resistance and HIV viral
load at baseline, there was no significant
change in viral loadlog 10 during the course of the
study (γslope = -0.590, t (79) = -1.08, p = .29).
• BUT there was a or significant differences
between conditions (γslope = 2.09, t (76) = 2.20, p = .03)
over the course of the study. This was a 61.2
DC4 cell increase compared to a 22.4 CD4 cell
decrease
Conclusions
• CBT-AD had acute and significant effects on
both adherence and depression during the
intervention for triply diagnosed HIV-infected
IDU
• Post-intervention discontinuation, adherence
rates decreased but improvements in
depression remained relatively stable
• Individuals struggling with multiple
comorbidities, such as substance abuse and
depression, may benefit from continued
adherence counseling even after depression
improves
•Integrated Life Steps Treatment Manuals
Thank You
Collaborators:
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Dr. Kenneth Mayer
Dr. Roger Weiss
Dr. Deb Herman
Dr. Nafisseh Soroudi
Dr. Robert Malow
Dr. Christina Psaros
Dr. Andres Bedoya
Dr. Jonathan Lerner
Dr. Jeffrey Gonzalez
Dr. Joseph Greer
Dr. Robert Knauz
Norma Reppucci
Joan Cremins
Susan Adams
Betty Bredin
Cal Dyer
Research Coordinators:
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Giselle Perez
Susie Michelson
Pamela Handelsman
Luis Serpa
Laura Reilly
Jared Israel
Jackie Bullis
The Participants!
The Substance Abuse Treatment Clinics
Bay Cove
Habit OpCo
CSAC
NIDA Funding: R01 DA018603
Questions?